Differential DNA affinity specifies roles for the origin recognition complex in budding yeast heterochromatin

Genes Dev. 2003 Aug 1;17(15):1817-22. doi: 10.1101/gad.1096703.

Abstract

The origin recognition complex (ORC) marks chromosomal positions as replication origins and is essential for replication initiation. At a few loci, the ORC functions in heterochromatin formation. We show that the ORC's two roles at the heterochromatic HMRa locus in Saccharomyces cerevisiae were regulated by differences in the ORC's interaction with its target site. At HMRa, a strong ORC-DNA interaction inhibited and delayed replication initiation but promoted heterochromatin formation, whereas a weak ORC-DNA interaction allowed for increased and earlier replication initiation but reduced heterochromatin formation. Therefore, the ORC's interaction with its target site could modulate ORC activity within a heterochromatin domain in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Binding Sites
  • DNA / metabolism*
  • DNA-Binding Proteins
  • Gene Silencing
  • Heterochromatin / genetics*
  • Heterochromatin / metabolism*
  • Molecular Sequence Data
  • Origin Recognition Complex
  • Protein Binding
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae / metabolism
  • Time Factors

Substances

  • DNA-Binding Proteins
  • Heterochromatin
  • Origin Recognition Complex
  • DNA